20S-Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic stellate cell apoptosis through liver kinase B1-AMP-activated protein kinase activation |
Park, Sang Mi
(MRC-GHF, Department of Herbal Formulation, College of Korean Medicine, Daegu Haany University)
Jung, Eun Hye (MRC-GHF, Department of Herbal Formulation, College of Korean Medicine, Daegu Haany University) Kim, Jae Kwang (MRC-GHF, Department of Herbal Formulation, College of Korean Medicine, Daegu Haany University) Jegal, Kyung Hwan (MRC-GHF, Department of Herbal Formulation, College of Korean Medicine, Daegu Haany University) Park, Chung A (College of Korean Medicine, Daegu Haany University) Cho, Il Je (MRC-GHF, Department of Herbal Formulation, College of Korean Medicine, Daegu Haany University) Kim, Sang Chan (MRC-GHF, Department of Herbal Formulation, College of Korean Medicine, Daegu Haany University) |
1 | Zhai X, Qiao H, Guan W, Li Z, Cheng Y, Jia X, Zhou Y. Curcumin regulates peroxisome proliferator-activated receptor- coactivator- expression by AMPK pathway in hepatic stellate cells in vitro. Eur J Pharmacol 2015;746:56-62. DOI |
2 | Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006;124:471-84. DOI |
3 | Shaw RJ. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol 2009;196:65-80. DOI |
4 | Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008;30:214-26. DOI |
5 | Djouder N, Tuerk RD, Suter M, Salvioni P, Thali RF, Scholz R, Vaahtomeri K, Auchli Y, Rechsteiner H, Brunisholz RA, et al. PKA phosphorylates and inactivates AMPKalpha to promote efficient lipolysis. EMBO J 2010;29:469-81. DOI |
6 | Kim SJ, Yuan HD, Chung SH. Ginsenoside Rg1 suppresses hepatic glucose production via AMP-activated protein kinase in HepG2 cells. Biol Pharm Bull 2010;33:325-8. DOI |
7 | Hien TT, Kim ND, Pokharel YR, Oh SJ, Lee MY, Kang KW. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase. Toxicol Appl Pharmacol 2010;246:171-83. DOI |
8 | Kim DY, Park MW, Yuan HD, Lee HJ, Kim SH, Chung SH. Compound K induces apoptosis via CAMK-IV/AMPK pathways in HT-29 colon cancer cells. J Agric Food Chem 2009;57:10573-8. DOI |
9 | Moreira RK. Hepatic stellate cells and liver fibrosis. Arch Pathol Lab Med 2007;131:1728-34. |
10 | Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005;115:209-18. DOI |
11 | Lee YA, Wallace MC, Friedman SL. Pathobiology of liver fibrosis: a translational success story. Gut 2015;64:830-41. DOI |
12 | Wang N, Xu Q, Tan HY, Hong M, Li S, Yuen MF, Feng Y. Berberine inhibition of fibrogenesis in a rat model of liver fibrosis and in hepatic stellate cells. Evid Based Complement Alternat Med 2016;2016:8762345. |
13 | Ko HL, Jung EH, Jung DH, Kim JK, Ku SK, Kim YW, Kim SC, Zhao R, Lee CW, Cho IJ. Paeonia japonica root extract protects hepatocytes against oxidative stress through inhibition of AMPK-mediated . J Funct Foods 2016;20:303-16. DOI |
14 | Kim BH, Yoon JH, Yang JI, Myung SJ, Lee JH, Jung EU, Yu SJ, Kim YJ, Lee HS, Kim CY. Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis. J Gastroenterol Hepatol 2013;28:1859-68. DOI |
15 | Lage R, Dieguez C, Vidal-Puig A, Lopez M. AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol Med 2008;14:539-49. DOI |
16 | Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 2005;1:15-25. DOI |
17 | Egan D, Kim J, Shaw RJ, Guan KL. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy 2011;7:643-4. DOI |
18 | Caligiuri A, Bertolani C, Guerra CT, Aleffi S, Galastri S, Trappoliere M, Vizzutti F, Gelmini S, Laffi G, Pinzani M, et al. Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells. Hepatology 2008;47:668-76. |
19 | Lim JY, Oh MA, Kim WH, Sohn HY, Park SI. AMP-activated protein kinase inhibits TGF--induced fibrogenic responses of hepatic stellate cells by targeting transcriptional coactivator p300. J Cell Physiol 2012;227:1081-9. DOI |
20 | Adachi M, Brenner DA. High molecular weight adiponectin inhibits proliferation of hepatic stellate cells via activation of adenosine monophosphateactivated protein kinase. Hepatology 2008;47:677-85. DOI |
21 | Wang CZ, Zhang Z, Wan JY, Zhang CF, Anderson S, He X, Yu C, He TC, Qi LW, Yuan CS. Protopanaxadiol, an active ginseng metabolite, significantly enhances the effects of fluorouracil on colon cancer. Nutrients 2015;7:799-814. DOI |
22 | Ding X, Saxena NK, Lin S, Xu A, Srinivasan S, Anania FA. The roles of leptin and adiponectin: a novel paradigm in adipocytokine regulation of liver fibrosis and stellate cell biology. Am J Pathol 2005;166:1655-69. DOI |
23 | Kim DH. Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res 2012;36:1-15. DOI |
24 | Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93. DOI |
25 | Wan JY, Liu P, Wang HY, Qi LW, Wang CZ, Li P, Yuan CS. Biotransformation and metabolic profile of American ginseng saponins with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry. J Chromatogr A 2013;1286:83-92. DOI |
26 | Bae EA, Park SY, Kim DH. Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull 2000;23:1481-5. DOI |
27 | Jeong KJ, Kim GW, Chung SH. AMP-activated protein kinase: an emerging target for ginseng. J Ginseng Res 2014;38:83-8. DOI |
28 | Hasegawa H, Sung JH, Matsumiya S, Uchiyama M. Main ginseng saponin metabolites formed by intestinal bacteria. Planta Med 1996;62:453-7. DOI |
29 | Xin Y, Wei J, Chunhua M, Danhong Y, Jianguo Z, Zongqi C, Jian-An B. Protective effects of ginsenoside Rg1 against carbon tetrachloride-induced liver injury in mice through suppression of inflammation. Phytomedicine 2016;23:583-8. DOI |
30 | Han JY, Lee S, Yang JH, Kim S, Sim J, Kim MG, Jeong TC, Ku SK, Cho IJ, Ki SH. Korean Red Ginseng attenuates ethanol-induced steatosis and oxidative stress via AMPK/Sirt1 activation. J Ginseng Res 2015;39:105-15. DOI |
31 | Yuan HD, Kim DY, Quan HY, Kim SJ, Jung MS, Chung SH. Ginsenoside Rg2 induces orphan nuclear receptor SHP gene expression and inactivates via AMP-activated protein kinase to inhibit hepatic glucose production in HepG2 cells. Chem Biol Interact 2012;195:35-42. DOI |
32 | Hou YL, Tsai YH, Lin YH, Chao JC. Ginseng extract and ginsenoside Rb1 attenuate carbon tetrachloride-induced liver fibrosis in rats. BMC Complement Altern Med 2014;14:415. DOI |
33 | Geng J, Peng W, Huang Y, Fan H, Li S. Ginsenoside-Rg1 from Panax notoginseng prevents hepatic fibrosis induced by thioacetamide in rats. Eur J Pharmacol 2010;634:162-9. DOI |
34 | Park EJ, Zhao YZ, Kim J, Sohn DH. A ginsenoside metabolite, 20-O-beta-dglucopyranosyl-20(S)-protopanaxadiol, triggers apoptosis in activated rat hepatic stellate cells via caspase-3 activation. Planta Med 2006;72:1250-3. DOI |
35 | Ki SH, Yang JH, Ku SK, Kim SC, Kim YW, Cho IJ. Red ginseng extract protects against carbon tetrachloride-induced liver fibrosis. J Ginseng Res 2013;37:45-53. DOI |
36 | Xu H, Yu X, Qu S, Chen Y, Wang Z, Sui D. Protective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins, isolated from Panax quinquefolium, on permanent focal cerebral ischemic injury in rats. Exp Ther Med 2014;7:165-70. DOI |
37 | Cho IJ, Kim YW, Han CY, Kim EH, Anderson RA, Lee YS, Lee CH, Hwang SJ, Kim SG. E-cadherin antagonizes transforming growth factor gene induction in hepatic stellate cells by inhibiting RhoA-dependent Smad3 phosphorylation. Hepatology 2010;52:2053-64. DOI |
38 | Bae EA, Han MJ, Choo MK, Park SY, Kim DH. Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 2002;25:58-63. DOI |
39 | Shin DJ, Kim JE, Lim TG, Jeong EH, Park G, Kang NJ, Park JS, Yeom MH, Oh DK, Bode AM, et al. 20-O--d-Glucopyranosyl-20(S)-protopanaxadiol suppresses UV-Induced MMP-1 expression through AMPK-mediated mTOR inhibition as a downstream of the PKA-LKB1 pathway. J Cell Biochem 2014;115:1702-11. DOI |
40 | Cao B, Qi Y, Yang Y, Liu X, Xu D, Guo W, Zhan Y, Xiong Z, Zhang A, Wang AR, et al. 20(S)-Protopanaxadiol inhibition of progression and growth of castration-resistant prostate cancer. PLoS One 2014;9:e111201. DOI |
41 | Kuo LM, Kuo CY, Lin CY, Hung MF, Shen JJ, Hwang TL. Intracellular glutathione depletion by oridonin leads to apoptosis in hepatic stellate cells. Molecules 2014;19:3327-44. DOI |
42 | Liu JJ, Huang RW, Lin DJ, Peng J, Wu XY, Lin Q, Pan XL, Song YQ, Zhang MH, Hou M, et al. Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-gamma ligands induces apoptosis on human myeloid leukemia cells in vitro. Annals Oncol 2005;16:455-9. DOI |
43 | Walsh JG, Cullen SP, Sheridan C, Luthi AU, Gerner C, Martin SJ. Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc Natl Acad Sci U S A 2008;105:12815-9. DOI |
44 | Zhang C, Liao Y, Li Q, Chen M, Zhao Q, Deng R, Wu C, Yang A, Guo Z, Wang D, et al. Recombinant adiponectin ameliorates liver ischemia reperfusion injury via activating the AMPK/eNOS pathway. PLoS One 2013;8:e66382. DOI |
45 | Herceg C, Wang ZQ. Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res 2001;477:97-110. DOI |
46 | Dong GZ, Jang EJ, Kang SH, Cho IJ, Park SD, Kim SC, Kim YW. Red ginseng abrogates oxidative stress via mitochondria protection mediated by LKB1-AMPK pathway. BMC Complement Altern Med 2013;13:64. DOI |
47 | Cai L, Hu K, Lin L, Ai Q, Ge P, Liu Y, Dai J, Ye B, Zhang L. AMPK dependent protective effects of metformin on tumor necrosis factor-induced apoptotic liver injury. Biochem Biophys Res Commun 2015;465:381-6. DOI |
48 | Cai X, Hu X, Cai B, Wang Q, Li Y, Tan X, Hu H, Chen X, Huang J, Cheng J, et al. Metformin suppresses hepatocellular carcinoma cell growth through induction of cell cycle G1/G0 phase arrest and p21CIP and p27KIP expression and downregulation of cyclin D1 in vitro and in vivo. Oncol Rep 2013;30:2449-57. DOI |
49 | Lee CW, Wong LL, Tse EY, Liu HF, Leong VY, Lee JM, Hardie DG, Ng IO, Ching YP. AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res 2012;72:4394-404. DOI |
50 | Lian N, Jin H, Zhang F, Wu L, Shao J, Lu Y, Zheng S. Curcumin inhibits aerobic glycolysis in hepatic stellate cells associated with activation of adenosine monophosphate-activated protein kinase. IUBMB Life 2016;68:589-96. DOI |